Generation of procoagulant collagen‐ and thrombin‐activated platelets in platelet concentrates derived from buffy coat: the role of processing, pathogen inactivation, and storage

Calderara, Debora Bertaggia; Crettaz, David; Aliotta, Alessandro; Barelli, Stefano; Tissot, Jean‐Daniel; Prudent, Michel; Alberio, Lorenzo

doi:10.1111/trf.14883

Cited by 11 publications

(14 citation statements)

References 61 publications

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“…Following adenosine diphosphate (ADP) stimulation, decreases of αIIbßIII activation and pselectin expression were clearly reported since the beginning of the storage. 27 Such results suggest a functional defect due to weak stimulation. The hypothesis is a desensitization of the ADP receptors because of previous exposition to ADP.…”

Section: Function Of Stored Plateletsmentioning

confidence: 98%

“…In buffy-coatderived PCs the percentages of COAT platelets were decreased from more than 30% to less than 10%. 27 By consequence, they were reported to be present at a lower level in PCs than in human. Decreases of COAT population were also observed to different extent in buffy-coat-derived PCs 38 and PCs from apheresis.…”

Section: Function Of Stored Plateletsmentioning

confidence: 99%

“…It increases after processing steps as well during the storage. [21][22][23][25][26][27] As for the PS exposure (usually quantified by binding to annexin V), the percentages increase and the effect is even exacerbated by the pathogen inactivation. It has to be noticed that the sample preparation influences the results.…”

Section: Phenotype Of Stored Plateletsmentioning

confidence: 99%

“…The hypothesis is a desensitization of the ADP receptors because of previous exposition to ADP. 27,31,32 These investigations enable scientists to monitor the reactivity of the platelets to activation and to investigate different cellular pathways.…”

Section: Function Of Stored Plateletsmentioning

confidence: 99%

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What about Platelet Function in Platelet Concentrates?

Prudent

2020

Hamostaseologie

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The characterization of platelet concentrates (PCs) in transfusion medicine has been performed with different analytical methods and platelet lesions (from biochemistry to cell biology) have been documented. In routine quality assessment and validation of manufacturing processes of PCs for transfusion purposes, only basic parameters are monitored and the platelet functions are not included. However, PCs undergo several manipulations during the processing and the basic parameters do not provide sensitive analyses to properly picture out the impact of the blood component preparation and storage on platelets. To improve the transfusion supply chain and the platelet functionalities, additional parameters should be used. The present short review will focus on the different techniques to monitor ex vivo platelet lesions from phenotype characterization to advanced omic analyses. Then, the opportunities to use these methods in quality control, process validation, development, and research will be discussed. Functional markers should be considered because they would be an advantage for the future developments in transfusion medicine.

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Section: Function Of Stored Plateletsmentioning

confidence: 98%

Section: Function Of Stored Plateletsmentioning

confidence: 99%

Section: Phenotype Of Stored Plateletsmentioning

confidence: 99%

Section: Function Of Stored Plateletsmentioning

confidence: 99%

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What about Platelet Function in Platelet Concentrates?

Prudent

2020

Hamostaseologie

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“…Indeed, why only a small fraction of (potentially) aggregating platelets further proceed to become procoagulant, despite a similar strong activation, is still not fully elucidated. 16 It is known that the procoagulant activity of the platelets can be modulated by ADP, [17][18][19][20][21][22][23] but not by thromboxane A2. 19 ADP amplifies the procoagulant response induced by collagen and thrombin through P2Y12 signalling.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

High-Dose Epinephrine Enhances Platelet Aggregation at the Expense of Procoagulant Activity

et al. 2021

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Platelet activation is characterized by shape change, granule secretion, activation of fibrinogen receptor (glycoprotein [GP] IIb/IIIa) sustaining platelet aggregation, and externalization of negatively charged aminophospholipids contributing to platelet procoagulant activity. Epinephrine alone is a weak platelet activator. However, it is able to potentiate platelet activation initiated by other agonists. In this work, we investigated the role of epinephrine in the generation of procoagulant platelets. Human platelets were activated with convulxin (CVX), thrombin (THR) or protease-activated receptor (PARs) agonists, epinephrine (EPI), and combination thereof. Platelet aggregation was assessed by light transmission aggregometry or with PAC-1 binding by flow cytometry. Procoagulant collagen-and-thrombin (COAT) platelets, induced by combined activation with CVX-and-THR, were visualized by flow cytometry as Annexin-V-positive and PAC-1-negative platelets. Cytosolic calcium fluxes were monitored by flow cytometry using Fluo-3 indicator. EPI increased platelet aggregation induced by all agonist combinations tested. On the other hand, EPI dose-dependently reduced the formation of procoagulant COAT platelets generated by combined CVX-and-THR activation. We observed a decreased Annexin-V positivity and increased binding of PAC-1 with the triple activation (CVX+THR+EPI) com-pared with CVX+THR. Calcium mobilization with triple activation was decreased with the higher EPI dose (1000 µM) compared with CVX+THR calcium kinetics. In conclusion, when platelets are activated with CVX-and-THR, the addition of increasing concentrations of EPI (triple stimulation) modulates platelet response reducing cytosolic calcium mobilization, decreasing procoagulant activity and en-hancing platelet aggregation.

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General overview of blood products in vitro quality: Processing and storage lesions

Abonnenc

Tissot

Prudent

2018

Transfusion Clinique et Biologique

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Generation of procoagulant collagen‐ and thrombin‐activated platelets in platelet concentrates derived from buffy coat: the role of processing, pathogen inactivation, and storage

Abstract: Preparation of PCs from buffy coats decreased the ability to generate COAT PLTs and impaired PLT response to ADP.

Cited by 11 publications

References 61 publications

What about Platelet Function in Platelet Concentrates?

What about Platelet Function in Platelet Concentrates?

High-Dose Epinephrine Enhances Platelet Aggregation at the Expense of Procoagulant Activity

General overview of blood products in vitro quality: Processing and storage lesions

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